The Missouri senator scored her first victory of the race when Todd Akin won a three-way primary. Among the GOP field, Akin polled the worst against McCaskill in potential general-election matchups. Seeing an opportunity, McCaskill aired TV ads in the state that purported to attack Akin, but lauded his conservative credentials in a not-so-subtle attempt to bolster him in the primary.

McCaskill won her second victory when Akin made his fateful “legitimate rape” comment in August — the biggest misstep by any candidate in 2012, one that reverberated throughout other Republican races and drew Akin condemnation from the highest levels of his party.

Mitt Romney, Senate Minority Leader Mitch McConnell and National Republican Senatorial Committee Chairman John Cornyn all called on Akin to exit his race.

The incumbent won her third major victory on Sept. 25, when Akin officially weathered the pressure to exit and remained the GOP’s candidate — whether they liked it or not — with the passage of his withdrawal deadline.

Akin made strides to recover from his big mistake, working to shore up support among social conservatives and telling Missouri voters that he agreed with them on most issues. But it wasn’t enough.

Republicans had eyed Missouri as a prime pickup opportunity from the beginning of the election cycle. Faced with 23 Democratic Senate seats and only 10 Republican seats up for election, Missouri figured into their expectation of moving a chunk of the Senate into the red column, possibly enough to retake control of the Senate.

But “rape” comments might have proved their undoing in two states. After Akin made national headlines, Indiana treasurer Richard Mourdock made his own when he suggested pregnancies from rape were something “God intended.”

Republicans’ problem in Indiana might have more to do with unseating a six-term incumbent, Sen. Dick Lugar, with the tea-partier Mourdock in a primary taking a safe GOP candidate off the board. But “rape” was the issue in Missouri.

Women voted 56 percent for McCaskill, who won 67 percent of the moderate vote. Akin’s comment clearly helped McCaskill capture the middle: 21 percent of voters said Akin’s “rape” comment was the single most important issue for them when they voted, while 40 percent said it was one of several important factors.

Akin made his plea for Missouri voters to forgive and forget. But in a state that’s considered more red than purple, a major misstep has cost Republicans a vital vote in the Upper Chamber.